1999 Fiscal Year Final Research Report Summary
Host factors involved in development of poliomyelitis
| Project/Area Number |
07102005
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| Research Category |
Grant-in-Aid for Specially Promoted Research
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | The University of Tokyo |
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Principal Investigator |
NOMOTO Akio Institute of Medical Science, The University of Tokyo, Professor, 医科学研究所, 教授 (70112670)
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| Project Period (FY) |
1995 – 1999
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| Keywords | poliovirus / mouse model / poliovirus receptor / pathogenesis / dissemination / IRES / axonal transport / host |
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| Research Abstract |
Poliovirus (PV) infection induced change in patterns of two-dimensional gel electrophoresis of total proteins of HeLa cells. Identification of proteins of these spots is now being investigated.
To support our idea of "IRES (internal ribosome entry site)-dependent virus tropism", a chimera PV, in which PV IRES is replaced by hepatitis C virus (HCV) IRES, was constructed. The chimera virus was examined for its replication ability in the liver and the central nervous system (CNS) of poliovirus-sensitive transgenic mice. Replication rate of the chimera virus was compared with that of the parental PV. The results have suggested that PV IRES works both in the liver and CNS, and that HCV IRES works in the liver but not in the CNS.
We demonstrated that interaction of the cytoplasmic domain (cyto) of human PV receptor (hPVR) with cytoplasmic dynein light chain 1 may have an important role in retrograde axonal transport of PV. To identify key amino acids of hPVR-cyto involved in the interaction, a
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series of deletion mutants of hPVR-cyto were constructed and tested for their binding activity to dynein molecule. The results suggested that N-terminal 20 amino acids of hPVR-cyto were essential for the interaction.
The hPVR has been thought to have a dual function, that is, binding ability to PV and conformation alteration ability of PV particle. To know how these two abilities contribute to establishment of PV infection, mouse cell line expressing Fcγ receptor was established and named LmFcRI cell line. As mediators of PV and LmFcRI cells, several anti-PV monoclonal antibodies and PVR-IgG2a which is a fusion protein of the extracellular domain of hPVR and Fc portion of mouse IgG2a was used. The results have suggested that binding of PV on the cell surface induces PV infection at very low level, and that specific interaction of hPVR with PV affords a high level of infectivity to PV. This enhancement of infectivity induced by hPVR may be essential for establishment of PV infection in a whole body. Less
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[Publications] Shiroki, K., Isoyama, T., Kuge, S., Ishii, T., Ohmi, S., Hata, S., Suzuki, K., Takasaki, Y., and Nomoto, A.: "Intracellular redistribution of truncated La protein produced by poliovirus 3CPRO-mediated cleavage"J. Virol.. 73(3). 2193-2200 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Isoyama, T., Kamoshita, N., Yasui, K., Iwai, A., Shiroki, K., Toyoda. H., Yamada, A., and Nomoto, A.: "Lower concentration of La protein required for internal ribosome entry on hepatitis C virus RNA than poliovirus RNA"J. Gen. Virol.. 80(9). 2319-2327 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Kuge, S., Nomoto, A., and Jones, N.: "Regulation of yAP-1 nuclear localization in response to oxidative stress"In Redox Regulation of Cell Signaling and Its Clinical Application, Lester Packer, Junji Yodoi, eds., Marcel Dekker, Inc., New York, Basel. 73-84 (1999)
Description
「研究成果報告書概要(欧文)」より
